受体酪氨酸激酶EphB1在胃癌中的表达及其临床意义

Expression and its clinical significance of receptor tyrosine kinase EphB1 in gastric carcinoma

背景与目的:受体酪氨酸激酶Eph基因家族在神经和脉管系统发育中发挥重要作用,也可能参与某些肿瘤的发生、进展和预后。本研究探讨该家族成员EphB1在胃癌组织中的表达及其临床意义。方法:应用实时定量RT-PCR(real-time reverse-transcriptase PCR)测定61例胃癌组织标本(包括来源于同一患者的正常黏膜和癌组织)和5株胃癌细胞的EphB1mRNA。并应用抗EphB1的特异性多克隆抗体对其中58例进行免疫组化染色,探讨EphB1蛋白在正常黏膜和肿瘤细胞中的表达水平及细胞内定位。结果:EphB1mRNA在胃癌细胞株中呈现不同程度表达。与正常黏膜相比,69%(42/61)的患者胃癌组织EphB1mRNA表达上调,15%(9/61)的患者表达下调,16%(10/61)的患者标本中表达既不上调也不下调。EphB1mRNA表达与患者的性别、肿瘤大小和淋巴结转移有关(P值分别为0.006,0.04和0.039),而与其他临床病理指标无关。EphB1蛋白表达水平与mRNA表达不完全一致。EphB1蛋白在45%(26/58)的患者标本中表达下调,在17%(10/58)的患者中上调,其余标本中表达既不上调也不下调。肿瘤细胞EphB1蛋白丢失与胃壁侵犯深度、分期和淋巴结转移呈正相关(P值分别为0.039,0.001和0.008)。结论:在胃癌进展过程中,EphB1可能发挥肿瘤抑制作用。它有可能成为胃癌预后的新标志物及基因治疗的新靶标。

Background and purpose： The Eph family of receptor tyrosine kinases plays an important role in the development of the nervous and vascular systems, and may be involved in carcinogenesis, progression and prognosis of certain cancers. This study aimed to investigate the expression and clinical significance of EphB 1 subfamily in gastric cancer.. Methods： Quantitative real-time reverse-transcriptase PCR was used to detect expression levels of EphB 1 mRNA in 61 specimens of gastric carcinomas （normal mucosa and carcinoma tissue from the same patient） and 5 gastric cancer cell lines, Immunohistochemistry with a specific polyclonal anti-EphB 1 antibody was conducted in 58 tissue specimens to investigate the expression and subcellular location in normal and gastric cancer cells. Results： EphB 1 mRNA were differentially expressed in gastric cancer cell lines. Comparing with normal mucosa, EphB 1 mRNA was up-regulated in 69% （42/61） and down-regulated in 15% （9/61） of the tested tumor samples. There was no difference in 16% （10/61） of the samples. The mRNA level of EphB1 was significantly related to gender, tumor size and lymph node metastasis （P=0.006, 0.04 and 0.039, respectively）. The expression level of the EphB 1 protein was not completely consistent with that of mRNA. Up- and down-regulation were detected in 17% （10/58） and 45% （26/58） of the samples, respectively; and no difference was detected in other samples. The loss of EphB1 protein was positively related to the depth of invasion, stage and metastasis of tumor （P=0.039, 0.001 and 0.008）. Conclusion： EphB 1 may be a tumor suppressor in progression of gastric carcinoma, and a new marker for prognosis of gastric cancer, it may also serve as a new target for gene therapy.